Preparation and the in-vivo evaluation of paclitaxel liposomes for lung targeting delivery in dogs

J Pharm Pharmacol. 2011 Jan;63(1):80-6. doi: 10.1111/j.2042-7158.2010.01184.x.

Abstract

Objectives: The aim of this study was to develop paclitaxel liposomes for a lung targeting delivery system.

Methods: The liposomes composed of Tween-80/HSPC/cholesterol (0.03 : 3.84 : 3.84, mol/mol), containing paclitaxel and lipids (1 : 40, mol/mol), were prepared by a combination of solid dispersion and effervescent techniques, and then subjected to ultrasonication. The pharmacokinetics and biodistribution of liposomal and injectable formulation of paclitaxel in dogs were studied after intravenous administration.

Key findings: The mean diameter, polydispersity index, zeta-potential and entrapment efficiency of the liposomes were 501.60 ± 15.43 nm, 0.28 ± 0.02, -20.93 ± 0.06 mV and 95.17 ± 0.32%, respectively. The liposomal formulation kept stable for at least 3 months at 6 ± 2°C and didn't cause haemolysis. The liposome carrier decreased the area under the curve and terminal half-life of paclitaxel compared with paclitaxel injection ranging from 0.352 ± 0.031 mg/l*h and 0.0671 ± 0.144 h to 0.748 ± 0.062 mg/l*h and 1.978 ± 0.518 h, respectively. The paclitaxel liposomes produced a drug concentration in the lung that was markedly higher than that in other organs or tissues and was about 15-fold of that of paclitaxel injection at 2 h.

Conclusions: To sum up, these results demonstrated that the paclitaxel liposomes are an effective lung targeted carrier in the treatment of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Area Under Curve
  • Cholesterol / chemistry
  • Dogs
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Stability
  • Drug Storage
  • Half-Life
  • Liposomes
  • Lung / metabolism*
  • Lung Neoplasms / drug therapy
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacokinetics*
  • Particle Size
  • Phosphatidylcholines / chemistry
  • Polysorbates / chemistry
  • Tissue Distribution
  • Ultrasonics

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Liposomes
  • Phosphatidylcholines
  • Polysorbates
  • Cholesterol
  • Paclitaxel